75 articles - From Saturday Mar 12 2022 to Friday Mar 18 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Blood |
| CA Cancer J Clin |
American Cancer Society nutrition and physical activity guideline for cancer survivors. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Adoptive therapy with CMV-specific T cells for CMV infection after haploidentical stem cell transplantation and factors affecting efficacy. In multivariate analysis, persistent CMV infection prior to CMV-CTL infusion (HR 2.29, 95% CI 1.29-4.06, P=0.005) and basiliximab treatment within 2 |
Health-related quality of life in patients with AL amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone ± daratumumab: results from the ANDROMEDA study. After cycle 6, patients in the D-VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health-related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent-to-treat population. These results demonstrate that the previously reported clinical benefits of D-VCd were achieved without decrement to patients' HRQoL and provide support of D-VCd in patients with AL amyloidosis. |
Mental Health Among Patients with non-Hodgkin Lymphoma: a Danish Nationwide Study of Psychotropic Drug Use in 8,750Patients and 43,750 Matched Comparators. NHL patients had a slightly higher two-year risk of suicide/intentional self-harm (0.3%) as compared to the matched comparators (0.2%, p=0.01). These results demonstrate that mental health complications among NHL patients are frequent. Routine assessment for symptoms of depression and anxiety should be consider as part of standard follow-up of NHL patients. |
| Ann Oncol |
Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel. Patients with CD experienced an 8-fold increased risk of small bowel adenocarcinomas, while both UC and CD patients experienced an about 2-fold increased risk of neuroendocrine tumors, and UC patients experienced 2-fold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective. |
| Blood |
Combining nilotinib and PD-L1 blockade reverses CD4+ T-cell dysfunction and prevents relapse in acute B-cell leukemia. Depletion of CD4+ T-cells prior to therapy completely abrogates the survival benefit, implicating CD4+ T-cells as key drivers of the protective anti-leukemia immune response. Indeed, treatment with anti-PD-L1 leads to clonal expansion of leukemia-specific CD4+ T-cells with the afore-mentioned helper/cytotoxic phenotype, as well as reduced expression of exhaustion markers. These findings support efforts to utilize PD1/PD-L1 checkpoint blockade in clinical trials and highlight the importance of CD4+ T-cell dysfunction in limiting the endogenous anti-leukemia response. |
Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis. Loss of hemogen in E12.5-E16.5 fetal liver cells impeded erythroid differentiation through reducing the production of mature erythroblasts. ChIP-seq in WT and hemogen KO animal revealed BRG1 is largely dependent on hemogen to regulate chromatin accessibility at erythroid gene promoters and enhancers. In summary, hemogen/BRG1 interaction in mammals is essential for fetal erythroid maturation and hemoglobin production through its active role in promoter and enhancer activity and chromatin organization. |
HMGA1 Chromatin Regulators Induce Transcriptional Networks Involved in GATA2 and Proliferation During MPN Progression. Further, HMGA1 transcriptional networks, including proliferation pathways and GATA2, are activated in human MF and MPN leukemic transformation. Importantly, HMGA1 depletion enhances responses to the JAK2 inhibitor, ruxolitinib, preventing MF and prolonging survival in murine models of JAK2V617F AML. These findings illuminate HMGA1 as a key epigenetic switch involved in MPN transformation and promising therapeutic target to treat or prevent disease progression. |
How I manage pregnancy in women with Glanzmann thrombasthenia. The newborn may also be affected by fetal and neonatal immune thrombocytopenia induced by the transplacental passage of maternal anti-aIIbß3 antibodies, which can lead to severe hemorrhage and fetal loss. Pregnancy in GT women thus requires a multidisciplinary approach, including prepregnancy counseling, and a treatment plan for delivery for both the mother and child. In this article, we summarize the current knowledge on pregnancy in women with GT and describe how we manage this severe platelet disorder in our clinical practice. |
Impact of diagnostic genetics on remission MRD and transplantation outcomes in older AML patients. However, in a multivariable model accounting for baseline risk, MRD-positivity had no independent impact on LFS, likely due to its significant association with diagnostic genetic characteristics including MDS-associated gene mutations, TP53 mutations, and high-risk karyotype. In conclusion, molecular associations with MRD positivity and transplant outcomes in older AML patients are driven primarily by baseline genetics, and not by mutations present in remission. In this group of patients, where high-intensity conditioning carries substantial risk of toxicity, alternative approaches to mitigating MRD-associated relapse risk are required. |
| Blood Adv |
CEACAM1 is a novel culture-compatible surface marker of expanded long-term reconstituting hematopoietic stem cells. In this article, we identify CEACAM1 as a novel culture-compatible surface marker of ex vivo expanded LT-HSCs that further refines the immuno-phenotype of these cells. CEACAM1-expressing cells show clonogenic and differentiation properties that are reminiscent of LT-HSCs in vitro, as well as long-term, serial and multilineage engraftment capacity in vivo. Sorting CEACAM1 expressing cells from the CD34+CD45RA-CD90+EPCR+ITGA3+ subset allows LT-HSC purification with incomparable purity, highlighting the value of this new marker. |
Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity. Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/ml) of anti-RBD-S1 IgG 5-6 months after the second vaccine dose (OR 8.2, P=0.007, Fisher's exact test). We conclude that while allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses. This trial is registered at EudraCT as 2021-000349-42. |
Donor-recipient sex is associated with transfusion-related outcomes in critically ill patients. There was a trend towards increased ARDS in patients receiving RBC from female donors compared to those receiving blood from males (p-value = 0.06) while AKI was higher in donor-recipient sex-matched transfusion groups compared to sex-mismatched groups (p-value = 0.05). This was an exploratory study with potential uncontrolled confounders that limits broad generalization of the findings. Results warrant further studies investigating biological mechanisms underlying the association between donor sex with adverse outcomes as well as studies on the benefit of matching of blood between donor and recipient. |
Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Results of the main+extension parts of these trials were consistent with the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypes. Trials registered at (NCT03196284; NCT03196297). |
Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice. The current study was designed to address these issues through longitudinal dose-response evaluation of four AAV vector candidates encoding two different FVIII transgenes in a murine model of hemophilia A. Plasma FVIII activity and anti-FVIII antibody data were used to generate a pharmacokinetic model that 1) identifies initial FVIII expression kinetics as the dominant risk factor for inhibitor development, 2) predicts a therapeutic window where immune tolerance is achieved, and 3) demonstrates evidence of gene therapy-based immune tolerance induction. While there are known limitations to the predictive value of preclinical immunogenicity testing, these studies can uncover or support the development of design principles that can guide the development of safe and effective genetic medicines. |
Platelet Proteomics to Understand the Pathophysiology of Immune Thrombocytopenia: Studies in Mouse Models. While most of the proteomic alterations were common to both ITP models, there were model-specific protein dynamics, which accompanied and explained alterations in platelet aggregation responses, as measured in the passive ITP model. Interestingly, the expression dynamics observed in Syk, may explain, extrapolated to human and pending validation, the increased bleeding tendency of ITP patients when treated with Fostamatinib as third-or-later-line, as opposed to second-line treatment. We propose that the platelet proteome may give diagnostic/prognostic insights into ITP, and such studies should be pursued in humans. |
Targeting hypersialylation in multiple myeloma represents a novel approach to enhance NK cell-mediated tumor responses. Additionally, we show that MM cells with low CD38 expression can be treated with al trans-retinoic acid (ATRA), SIA and Daratumumab to elicit a potent NK cell cytotoxic response. Finally, we demonstrate that Siglec-7KO potentiates NK cell cytotoxicity against Siglec-7L+ MM cells. Taken together, our work shows that desialylation of MM cells is a promising novel approach to enhance NK cell efficacy against MM, which can be combined with frontline therapies to elicit a potent anti-MM response. |
The differential role of the lipid raft-associated protein flotillin 2 for progression of myeloid leukemia. Inhibition of CDC42 by ML141 impaired the homing of CML LIC and, thereby, CML progression. This suggested that alteration of both CD44 and CDC42 may be causative of impaired CML progression in absence of FLOT2. In summary, our data suggest a FLOT2-CD44-CDC42 axis, which differentially regulates CML versus AML progression, with deficiency of FLOT2 impairing the development of CML. |
| Haematologica |
A self-assembled leucine polymer sensitizes leukemic stem cells to chemotherapy by inhibiting autophagy in acute myeloid leukemia. Notably, the leucine polymer and Leu-DOX were specifically uptaken by AML cells and LSCs but not by normal hematopoietic cells and hematopoietic stem/progenitor cells in the bone marrow. Consequently, Leu-DOX efficiently reduced LSCs and prolonged the survival of AML mice, with limited myeloablation and tissue damage side effects than DOX treatment. Overall, we proposed that the newly developed Leu-DOX is an effective autophagy inhibitor and an ideal drug to efficiently eliminate LSCs, thus serving as a revolutionary strategy to enhance the chemotherapy efficacy in AML. |
Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial. Using a multiparametric flow cytometry (MFC) assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients affected with Acute Myeloid Leukemia (AML). This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined MRD threshold of 0.035% bone marrow residual leukemic cell (RLC) calculated on mononuclear cells, 154 (59%) were negative (MRD. |
Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets. Finally, selective MRP4 inhibition significantly reduced both the total area covered by thrombi and the average thrombus size by about 40% in a flow chamber model. In conclusion, selective MRP4 inhibition causes reduced platelet adhesion and thrombus formation under flow conditions. This finding is mechanistically supported by inhibition of integrin aIIbß3 activation, elevated VASP phosphorylation and reduced calcium influx, based on inhibited cyclic nucleotide and thromboxane transport as well as possible further mechanisms. |
Syndromes predisposing to leukemia are a major cause of inherited cytopenias in children. Twelve patients had cytopenias with no known leukemia predisposition, including nine children with inherited thrombocytopenia and three with congenital neutropenia. In summary, almost one-third of 189 children referred with persistent cytopenias had an underlying inherited disorder; 79.7% of whom had a germline predisposition to leukemia. Precise diagnosis of children with cytopenias should direct follow-up and management programs and may positively impact disease outcome. |
| Leukemia |
Bone marrow clonal hematopoiesis is highly prevalent in blastic plasmacytoid dendritic cell neoplasm and frequently sharing a clonal origin in elderly patients. Karyotypic abnormalities were detected in 19/29(66%) BPDCN but only in 1/49 BM hematopoietic cells, providing additional evidence of clonal evolution. BM clonal hematopoiesis (CH) was associated with an older age (p |
In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Olaparib efficiently reduced overall engraftment and leukemia-initiating cell frequency as evident in serial transplantation assays in IDH1/2-mutant but not -wildtype AML/MDS PDXs. Importantly, we show that olaparib is effective in both IDH m i-naïve and -resistant AML PDXs, critical given the high relapse and refractoriness rates to IDH m i. Our pre-clinical studies provide a strong rationale for the translation of PARP inhibition to patients with IDH1/2-mutant AML/ MDS, providing an additional line of therapy for patients who do not respond to or relapse after targeted mutant IDH inhibition. |
| Thromb Haemost |
Clinical Delphi on aPLnegativization: report from the from the APS Study Group of the Italian Society for Rheumatology (SIR-APS). A substantial agreement exists among expert on how to define aPL negativization. VKA suspension should be embraced with extreme caution, particularly in case of previous thrombotic events and/or triple aPL positivity. Nevertheless, VKA cessation might be considered when risk factors are carefully monitored/treated and the presence for "extra criteria" is ruled out. |
Integrated GWAS and Gene Expression Suggest ORM1 as a Potential Regulator of Plasma Levels of Cell-Free DNA and Thrombosis Risk. Imputed genotypes, whole blood RNA-Seq data, and plasma cfDNA quantification were available for 935 of the GAIT-2 participants from 35 families with idiopathic thrombophilia. We performed heritability and GWAS analysis for cfDNA. The heritability of cfDNA was 0.26 ( in regulating cfDNA levels in plasma, which might contribute to the susceptibility to thrombosis through mechanisms of immunothrombosis. |
One Year Prevalence of Venous Thromboembolism in Hospitalized COVID-19 Patients in France: Patients' Characteristics, Time Trends, and Outcomes. Our study showed a decrease in the incidence of symptomatic VTE and PE in hospitalized COVID-19 patients, and a decreased time trend of outcomes during the second wave compared with the first one. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Natural killer cells - innate immune system as a part of adaptive immunotherapy in hematological malignancies. Advanced manufacturing processes are capable of producing NK cells relatively easily in large and clinically sufficient numbers, useable without subsequent manipulations or after genetic modifications, which can solve the lack of specificity and improve clinical efficacy of NK cell products. This review summarizes the basic characteristics of NK cells and provides a quick overview of their sources. Results of clinical trials in hematological malignancies are presented, and strategies on how to improve the clinical outcome of NK cell therapy are discussed. |
| Blood |
| CA Cancer J Clin |
Female erectile tissues and sexual dysfunction after pelvic radiotherapy: A scoping review. Articles were included in the review that involved normal female erectile tissues and radiotherapy side effects. The results show that little scientific investigation into the impacts of radiotherapy on female erectile tissues has been performed. Collaborative scientific investigations by clinical, basic, and behavioral scientists in oncology and radiotherapy are needed to generate radiobiologic and clinical evidence to advance prospective evaluation, prevention, and mitigation strategies that may improve sexual outcomes in female patients. |
| J Hematol Oncol |
Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. Surprisingly, recent preclinical studies have shown that upregulation of PD-L1 in the TME also improves the response and efficacy of immune checkpoint blockade. Immunotherapy is a promising anticancer strategy that provides novel insight into clinical applications. This review aims to guide the development of more effective and less toxic anti-PD-1/PD-L1 immunotherapies. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| J Hematol Oncol |
Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. Undetectable for sequencing, multiplex fluorochrome-guided competitive in vivo treatment trials identified a subset of relapse two clones as uniquely resistant to cytarabine treatment. Transcriptional and proteomic profiles obtained from resistant PDX clones and refractory AML patients defined a 16-gene score that was predictive of clinical outcome in a large independent patient cohort. Thus, we identified novel genes related to cytarabine resistance and provide proof of concept that intra-tumor heterogeneity reflects inter-tumor heterogeneity in AML. |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Leukemia |